{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T04:47:19Z","timestamp":1766551639105,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004071","name":"Khon Kaen University","doi-asserted-by":"publisher","award":["Research and Academic Services"],"award-info":[{"award-number":["Research and Academic Services"]}],"id":[{"id":"10.13039\/501100004071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012527","name":"Office of the Higher Education Commission","doi-asserted-by":"publisher","award":["Total Synthesis of Melatonin Project"],"award-info":[{"award-number":["Total Synthesis of Melatonin Project"]}],"id":[{"id":"10.13039\/100012527","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FCT - Foundation for Science and Technology","award":["UIDB\/04423\/2020 and UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020 and UIDP\/04423\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Pharm."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a common chronic neurodegenerative disorders. Melatonin (MLT) has been reported to be neuroprotective agent, and its modified structures exhibit potent antioxidant and anti-inflammation activities. Therefore, the activity of MLT and its derivatives against AD was investigated. Herein, the targeted enzymes, such as \u03b2-secretase (BACE1) and acetylcholinesterase (AChE), as well as the neuroprotective and neuritogenic effects on P19-derived neurons were evaluated. All the derivatives (1\u20135), including MLT, displayed potent inhibitory activity for BACE1, with inhibition values of more than 75% at 5 \u00b5M. A molecular docking study predicted that MLT, 5-MT, and 5 bound with BACE1 at catalytic amino acids Asp32 and the flap region, whereas 1\u20134 interacted with allosteric residue Thr232 and the flap region. The additional \u03c0-\u03c0 interactions between 2, 3, and 5 with Tyr71 promoted ligand-enzyme binding. In addition, MLT, 1, 3, and 5 significantly protected neuron cells from oxidative stress by increasing the cell viability to 97.95, 74.29, 70.80, and 69.50% at 1 nM, respectively. Moreover, these derivatives significantly induced neurite outgrowth by increasing the neurite length and number. The derivatives 1, 3, and 5 should be thoroughly studied as potential AD treatment and neuroprotective agents.<\/jats:p>","DOI":"10.3390\/scipharm88040058","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T11:59:00Z","timestamp":1607083140000},"page":"58","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["BACE1 Inhibitor, Neuroprotective, and Neuritogenic Activities of Melatonin Derivatives"],"prefix":"10.3390","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4675-7132","authenticated-orcid":false,"given":"Panyada","family":"Panyatip","sequence":"first","affiliation":[{"name":"Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Melatonin Research Group, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}]},{"given":"Sarin","family":"Tadtong","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Srinakharinwirot University, Nakhon-Nayok 26120, Thailand"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-4672","authenticated-orcid":false,"given":"Em\u00edlia","family":"Sousa","sequence":"additional","affiliation":[{"name":"CIIMAR, Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5069-2071","authenticated-orcid":false,"given":"Ploenthip","family":"Puthongking","sequence":"additional","affiliation":[{"name":"Melatonin Research Group, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1159\/000464422","article-title":"Molecular Pathogenesis of Alzheimer\u2019s Disease: An Update","volume":"24","year":"2017","journal-title":"Ann. 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